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The Association Between Global DNA Methylation and Telomere Length in a Longitudinal Study of Boilermakers
Author(s) -
Wong Jason Y. Y.,
De Vivo Immaculata,
Lin Xihong,
Grashow Rachel,
Cavallari Jennifer,
Christiani David C.
Publication year - 2014
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21796
Subject(s) - telomere , methylation , dna methylation , alu element , biology , genetics , andrology , dna , medicine , gene , gene expression , human genome , genome
The objectives of this study were to determine if global DNA methylation, as reflected in LINE‐1 and Alu elements, is associated with telomere length and whether it modifies the rate of telomeric change. A repeated‐measures longitudinal study was performed with a panel of 87 boilermaker subjects. The follow‐up period was 29 months. LINE‐1 and Alu methylation was determined using pyrosequencing. Leukocyte relative telomere length was assessed via real‐time qPCR. Linear‐mixed models were used to estimate the association between DNA methylation and telomere length. A structural equation model (SEM) was used to explore the hypothesized relationship between DNA methylation, proxies of particulate matter exposure, and telomere length at baseline. There appeared to be a positive association between both LINE‐1 and Alu methylation levels, and telomere length. For every incremental increase in LINE‐1 methylation, there was a statistically significant 1.0 × 10 −1 (95% CI: 4.6 × 10 −2 , 1.5 × 10 −1 , P < 0.01) unit increase in relative telomere length, controlling for age at baseline, current and past smoking status, work history, BMI (log kg/m 2 ) and leukocyte differentials. Furthermore, for every incremental increase in Alu methylation, there was a statistically significant 6.2 × 10 −2 (95% CI: 1.0 × 10 −2 , 1.1 × 10 −1 , P = 0.02) unit increase in relative telomere length. The interaction between LINE‐1 methylation and follow‐up time was statistically significant with an estimate −9.8 × 10 −3 (95% CI: −1.8 × 10 −2 , −1.9 × 10 −3 , P = 0.02); suggesting that the rate of telomeric change was modified by the degree of LINE‐1 methylation. No statistically significant association was found between the cumulative PM exposure construct, with global DNA methylation and telomere length at baseline.